The test had C-statistics of 0.824 to 0.874 for various cancer subtypes compared with controls; 0.8 or better on the 1-point scale is considered strong concordance, Peter Mazzone, MD, MPH, of the Cleveland Clinic, and colleagues found.

The test was dubbed a "colorimetric sensor assay" for its use of pigments on a disposable chip that change color in the presence of certain volatile compounds -- in this case, compounds previously linked to lung cancer.

Like all biomarkers for lung cancer so far, validation is needed in large clinical trials to prove that the tests not only work but are clinically useful, commented Gerard A. Silvestri, MD, of the Medical University of South Carolina in Charleston.

Still, he was optimistic that exhaled breath could hold the key to either prescreening to select truly high-risk individuals for low-dose CT scan programs or to triage suspicious nodules found on scans, to reduce harm from false positives.

"It's incredible. I don't understand why it hasn't taken off," Silvestri told MedPage Today. "If you could imagine the least invasive way to get an answer for patients, instead of having bronchoscopy or surgery or multiple biopsies, it would make so much sense."

The reason may be funding, Mazzone explained.

The technology is in the "valley of death" where it will fade away without getting picked up by companies to commercialize it, he said in an interview.

"The one advantage this biomarker could have over the others is once the models are developed, it's breathing in a machine and the answer comes up on the screen as opposed to sending a blood test away for a couple-thousand-dollar test, to come back a week or 2 later," he told attendees at the session.

His group's study included 236 high-risk patients over age 40 from two hospital systems, who had indeterminate lung nodules 4 to 20 mm in diameter that were either suspected as lung cancer awaiting biopsy, or biopsy-proven but untreated lung cancer.

Mazzone's group used tests on a separate set of 288 patients to optimize the system, making changes to the filters, sensors, and processing.

The final version had patients inhale through a filter eliminated outside volatile organic compounds. Then, triggered by end-tidal carbon dioxide, the device captured only the alveolar portion of the exhale so the final 4 L of breath passed across the sensor array.

The sensor array was imaged several times during and after the breath, with the colors converted to numerical vectors for red, green, blue, and ultraviolet spectrums.

Based on the pathology report or standard clinical follow-up, 81 of the validation set patients had cancer, with a range of stages and subtypes fitting the expected distribution.

The breath test results agreed fairly well with pathology or clinical findings. The C-statistics, also known as the area under the receiver operating characteristic curve, were:

0.828 for non-small cell lung cancer

0.824 for lung adenocarcinoma

0.874 for lung squamous cell carcinoma

Those figures were an improvement over the prior version of the test, which had C-statistics of 0.811 to 0.849, Mazzone pointed out.

The volatile organic compound profile can be considered a candidate biomarker but still has many steps to take before reaching the clinic, including technical validation of reliable performance and clinical validation in multicenter studies, Mazzone pointed out.

Silvestri called the group's careful, stepwise approach a good one but still warned that the needed large-scale trial could go either way.

"Sometimes when we see preliminary data from biomarkers it doesn't pan out when we start looking at a diverse population," he cautioned. "They can look so promising and not pan out."

Mazzone reported research support from Metabolomx, the company that makes the sensor tested, as well as Indi and the National Cancer Institute. He also reported consulting for Oncimmune and Varian.

Silvestri reported having no relevant disclosures.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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